WO1998033781A1 - Procede pour prevenir ou traiter l'hypertension due a une baisse de secretion de la renine, par l'administration d'un antagoniste de l'endotheline - Google Patents
Procede pour prevenir ou traiter l'hypertension due a une baisse de secretion de la renine, par l'administration d'un antagoniste de l'endotheline Download PDFInfo
- Publication number
- WO1998033781A1 WO1998033781A1 PCT/US1998/004229 US9804229W WO9833781A1 WO 1998033781 A1 WO1998033781 A1 WO 1998033781A1 US 9804229 W US9804229 W US 9804229W WO 9833781 A1 WO9833781 A1 WO 9833781A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- endothelin
- endothelin antagonist
- hypertension
- antagonist
- administering
- Prior art date
Links
- 0 CC(CC(*)(*(C)=*)NC)=O Chemical compound CC(CC(*)(*(C)=*)NC)=O 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/42—Oxazoles
- A61K31/421—1,3-Oxazoles, e.g. pemoline, trimethadione
Definitions
- the present invention relates to the prevention or treatment of low renin hypertension by administering an endothelin antagonist.
- Hypertension has a variety of etiologies. Due at least in part to this, the success of a pharmacological agent in treating one form of hypertension does not necessarily indicate that that agent will be successful in treating another form of hypertension.
- Renin is a protease which cleaves angiotensinogen to form angiotensin I, the latter which is then cleaved by a second enzyme (the angiotensin-converting enzyme or ACE) to form angiotensin II.
- ACE angiotensin-converting enzyme
- Administration of a pharmacological agent which inhibits renin or ACE, or which antagonizes the angiotensin II end-product of the cascade (“All antagonist"), can lower blood pressure and provide a route for the treatment of this form of hypertension ("essential hypertension”) which affects a large portion of the hypertensive patient population.
- Endothelin antagonists which are compounds capable, inter alia, of inhibiting the binding of endothelin peptides to endothelin receptors, are useful in the treatment of endothelin-related disorders. While certain such compounds have been described as having utility in the treatment of hypertension, the present invention provides a method employing these compounds specifically for the treatment of low renin hypertension.
- the present invention provides a method for the prevention or treatment of low renin hypertension in a mammal, comprising administering an endothelin antagonist to said mammal in an amount effective therefor.
- the endothelin antagonist employed may be any compound capable of inhibiting the action of endothelin peptides, especially, endothelin-1 (ET-1), endothelin-2 (ET-2) and/or endothelin-3 (ET-3).
- endothelin antagonists described in the following documents, incorporated herein by reference in their entirety, are exemplary of those contemplated for use in the present method: U.S. Patent No. 5,378,715; U.S. Patent No. 5,514,696; U.S. Patent No. 5,420,123; U.S. Application Serial No. 114,251, filed August 30, 1993; U.S. Application Serial No. 08/728,238, filed October 8, 1996; European Patent Application 702,012; U.S.
- SB 209670 a rationally designed potent nonpeptide endothelin receptor antagonist
- SB 217242 Ohlstein, E. H., et al., “Nonpeptide Endothelin Receptor Antagonists.
- TAK-044 (Masuda, Y., et al., "Receptor Binding and Antagonist Properties of a Novel Endothelin Receptor Antagonist, TAK-044 ⁇ CycloP- ⁇ -Aspartyl-3- [(4-Phenylpiperazin-l-yl)Carbonyl]-L-Alanyl-L- ⁇ -Aspartyl-D-2-(2- Thienyl)Glycyl-L-Leucyl-D-Tryptophyl]Disodium Salt ⁇ , in Human Endothelin A and Endothelin B Receptors", The Journal of Pharmacology and Experimental Therapeutics, Vol. 279(2), pp. 675-685 (1996)); bosentan
- Endothelin antagonists containing a sulfonamide moiety are preferred, particularly those described in European Patent Application 702,012, U.S. Application Serial No. 08/754,715, filed November 21, 1996, and U.S. Application Serial No. 60/035,832, filed January 30, 1997 by N.
- angiotensin II (AH) receptor antagonist including irbesartan, 2-n-butyl-4-spirocyclopentane-l-[(2'-(tetrazol-5-yl)biphenyl-4- yl)methyl]-2-imidazolin-5-one.
- AH angiotensin II
- the mammal may be any mammal subject to this malady, especially, a human.
- the endothelin antagonist may be administered in any suitable manner such as orally or parenterally, in an effective amount, such as within a dosage range of about 0.1 to about 100 mg/kg, preferably about 0.2 to about 50 mg/kg and more preferably about 0.5 to about 25 mg/kg (or from about 1 to about 2500 mg, preferably from about 5 to about 2000 mg) in single or 2 to 4 divided daily doses.
- the present invention also provides pharmaceutical compositions for the prevention or treatment of low renin hypertension, comprising an endothelin antagonist in an amount effective therefor and a pharmaceutically acceptable vehicle or diluent.
- the endothelin antagonist can be utilized in a composition such as tablet, capsule, sterile solution or suspension, compounded in a conventional manner with a physiologically acceptable vehicle or carrier, excipient, binder, preservative, stabilizer, flavor, etc. as called for by accepted pharmaceutical practice.
- the endothelin antagonist may, for example, be employed alone, in combination with one or more other endothelin antagonists, or with another compound useful for the treatment of low renin hypertension, such as neutral endopeptidase (NEP) inhibitors, for example, candoxatril and acetorphan; dual NEP-ACE inhibitors such as [4S- [4 ⁇ (R*), 7 ⁇ , 10a ⁇ ]]-octahydro-4-(2-mercapto-l-oxo-3- phenylpropyDamino] -5-oxo-7H-pyrido [2 , 1-b] [1 ,3] thiazepine-7-carboyxlic acid (BMS-186716, U.S.
- NEP neutral endopeptidase
- dual NEP-ACE inhibitors such as [4S- [4 ⁇ (R*), 7 ⁇ , 10a ⁇ ]]-octahydro-4-(2-mercapto-l-oxo-3- phen
- Patent No. 5,508,272 [S-(R*,R*)]-hexahydro-6-[(2- mercapto-l-oxo-3-phenylpropyl)amino]-2,2-dimethyl-7-oxo-lH-azepine-l- acetic acid (BMS-189921, U.S. Patent No.
- alatriopril alatriopril, sampatrilat, MDL 100240, and CGS 30440; diuretics, such as chlorothiazide, hydro chlorothiazide, flumethiazide, hydroflumethiazide, bendroflumethiazide, methylchlorothiazide, trichloromethiazide, polythiazide and benzothiazide as well as ethacrynic acid, tricrynafen, chlorthalidone, furosemide, musolimine, bumetanide, triamterene, amiloride and spironolactone and salts of such compounds; and calcium entry blockers such as amlodipine.
- such combination products preferably employ the endothelin antagonists within the dosage range described above and the other pharmaceutically active agent within its approved dosage range.
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU61878/98A AU6187898A (en) | 1997-01-30 | 1998-01-26 | Method for preventing or treating low renin hypertension by administering an endothelin antagonist |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US3582597P | 1997-01-30 | 1997-01-30 | |
US60/035,825 | 1997-01-30 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1998033781A1 true WO1998033781A1 (fr) | 1998-08-06 |
Family
ID=21884999
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US1998/004229 WO1998033781A1 (fr) | 1997-01-30 | 1998-01-26 | Procede pour prevenir ou traiter l'hypertension due a une baisse de secretion de la renine, par l'administration d'un antagoniste de l'endotheline |
Country Status (3)
Country | Link |
---|---|
US (1) | US5916907A (fr) |
AU (1) | AU6187898A (fr) |
WO (1) | WO1998033781A1 (fr) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022270487A1 (fr) | 2021-06-22 | 2022-12-29 | 株式会社アークメディスン | Composé, antagoniste du récepteur de l'endothéline-a et composition pharmaceutique |
Families Citing this family (10)
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US6743783B1 (en) * | 1993-12-01 | 2004-06-01 | Marine Polymer Technologies, Inc. | Pharmaceutical compositions comprising poly-β-1→4-N-acetylglucosamine |
US6638937B2 (en) | 1998-07-06 | 2003-10-28 | Bristol-Myers Squibb Co. | Biphenyl sulfonamides as dual angiotensin endothelin receptor antagonists |
WO2000071751A1 (fr) * | 1999-05-21 | 2000-11-30 | Myriad Genetics, Inc. | Gene du diabete |
US6902888B1 (en) | 1999-05-21 | 2005-06-07 | Myriad Genetics, Inc. | Diabetes gene |
AU2003270357A1 (en) * | 2002-09-06 | 2004-03-29 | Microbia, Inc. | Inhibitors of fungal invasion |
PL1750862T3 (pl) | 2004-06-04 | 2011-06-30 | Teva Pharma | Kompozycja farmaceutyczna zawierająca irbesartan |
EP2010167A2 (fr) * | 2006-04-13 | 2009-01-07 | Actelion Pharmaceuticals Ltd. | Traitement précoce de fibrose pulmonaire idiopathique |
WO2008103345A2 (fr) | 2007-02-19 | 2008-08-28 | Marine Polymer Technologies, Inc. | Compositions hémostatiques et régimes thérapeutiques |
NZ703163A (en) | 2010-04-15 | 2016-06-24 | Marinepolymer Tech Inc | Anti-bacterial applications of poly-n-acetylglucosamine nanofibers |
CA2832859C (fr) | 2011-04-15 | 2020-06-16 | Marine Polymer Technologies, Inc. | Traitement de maladies avec des nanofibres de poly-n-acetylglucosamine |
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1998
- 1998-01-26 AU AU61878/98A patent/AU6187898A/en not_active Abandoned
- 1998-01-26 WO PCT/US1998/004229 patent/WO1998033781A1/fr active Application Filing
- 1998-01-27 US US09/014,434 patent/US5916907A/en not_active Expired - Lifetime
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US5514691A (en) * | 1993-05-20 | 1996-05-07 | Immunopharmaceutics, Inc. | N-(4-halo-isoxazolyl)-sulfonamides and derivatives thereof that modulate the activity of endothelin |
EP0702012A1 (fr) * | 1994-08-26 | 1996-03-20 | Bristol-Myers Squibb Company | Biphényl sulfonamides et leur utilisation comme antagonistes de l'endothélin |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2022270487A1 (fr) | 2021-06-22 | 2022-12-29 | 株式会社アークメディスン | Composé, antagoniste du récepteur de l'endothéline-a et composition pharmaceutique |
KR20240022646A (ko) | 2021-06-22 | 2024-02-20 | 앨커메디신, 인크. | 화합물, 엔도텔린 a 수용체 길항제 및 의약 조성물 |
Also Published As
Publication number | Publication date |
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US5916907A (en) | 1999-06-29 |
AU6187898A (en) | 1998-08-25 |
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